Supplementary figures for MED13 dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver. Content: Figure S1. Cardiac overexpression of MED13 increases metabolic gene expression in white adipose tissue. Figure S. Regulation of liver metabolite production by cardiac expression of MED13 in the fed state. Figure S3. Cardiac overexpression of MED13 alters metabolic gene expression. Figure S4. MED13cTg hearts maintain the ability to adapt to fasting. Figure S5. Circulating factor(s) regulate enhanced WAT and liver metabolism and contribute to the lean phenotype of MED13cTg mice. Supplementary Table 1. Acylcarnitines in liver from fed and fasted and MED13cTg mice. SupplementaryTable. Acyl-CoAs in liver from fed and fasted and MED13cTg mice. SupplementaryTable 3. Acylcarnitines in heart from fed and fasted and MED13cTg mice. Supplementary Table 4. Acyl-CoAs in heart from fed and fasted and MED13cTg mice. SupplementaryTable 5. Acylcarnitines in serum from fed and fasted and MED13cTg mice. Supplemental figure legends
Supplementary Figure 1 A Fatty acid transport and oxidation Outer Mitochondrial Membrane / Cytoplasm Inner Mitochondrial Membrane Mitochondrial Matrix FFA ATP Acyl-CoA synthetase AMP (ACSL3) Acylcarnitine Carnitine palmitoyltransferase 1 (CPT1B) Carnitine palmitoyltransferase (CPTB) Fatty acid transporter (Slc7a) Acyl-CoA FADH (ACADVL) -Enoyl CoA FADH Acyl CoA Trifunctional protein (HADHA) Acyl-CoA,4-Dienoyl-CoA reductase + 3,-trans-enoyl-CoA isomerase NADP (ECH1) -Enoyl-CoA -Enoyl-CoA hydratase (ECHS1) 3-Hydroxyacyl-CoA 3-Ketoacyl CoA (plasma membrane) FFA 3-Hydroxyacyl-CoA FADH Malate Malate Fumarase Fumarate Pyruvate Citrate synthase Oxaloacetate (MDH) Succinate (SDHA) Succinate Pyruvate complex (DLAT, PDHX) GTP Krebs Cycle Succinyl CoA synthetase (SUCLA) Citrate Aconitase Succinyl CoA cis-aconitate Aconitase Isocitrate Isocitrate (IDH3A, IDH3G, IDH) α-ketoglutarate α-ketoglutarate complex (DLST) 3-Ketoacyl-CoA thiolase B Fold change over 8 6 4 Fatty acid oxidation genes ACSL13 CPT1b CPT ACADVL HADHA Ecl1 ECHS1 HADH Fold change over 6 4 DLAT PDHX Krebs cycle genes IDH3A IDH3G IDH DLST SUCLA SDHA MDH
Supplementary Figure A Concentration in liver (μm) C Liver ceramides (pmol/ml) D Heart ceramides (pmol/ml) 8 6 4 85 45 3. 5 4 1.5. 3 8 75 5 4 3 1 6 195 13 65 6 5 4 3 1 C14 C14 Lactate Pyruvate * C16 * * # C16 C18 * C18 Succinate * Fumarate C:1 C:1 Malate C C C C fed fasted fed fasted α-ketoglutarate Citrate C3 C3 * # *# C4:1 C4:1 B Concentration in heart (μm) C4 C4 63 43 3 1 3 1 C5 C5 Lactate C6:1 # C6:1 Pyruvate C6 C6 Succinate * d18:1/c16 d18:1/c16 Fumarate d18:1/c18 d18:1/c18 Malate d18:1/c d18:1/c α-ketoglutarate d18:1/c d18:1/c fed fasted fed fasted d18:1/c3 d18:1/c3 Citrate d18:1/c4:1 d18:1/c4:1 d18:1/c4 d18:1/c4 d18:1/c6:1 fed fasted fed fasted d18:1/c6:1 fed fasted fed fasted * d18:1/c6 d18:1/c6
SupplementaryFigure 3 A Fatty acid transport and oxidation Outer Mitochondrial Membrane / Cytoplasm Inner Mitochondrial Membrane Mitochondrial Matrix FFA ATP Acyl-CoA synthetase AMP (ACSL1) Acylcarnitine Carnitine palmitoyltransferase 1 (CPT1B) Carnitine palmitoyltransferase (CPT) FADH -Enoyl CoA FADH NADP Acyl CoA -Enoyl-CoA Fatty acid transporter Acyl-CoA Trifunctional protein (HADHA) (ADADM, ACADSB) -Enoyl-CoA hydratase (ECHS1) 3-Hydroxyacyl-CoA 3-Ketoacyl CoA (plasma membrane) Acyl-CoA,4-Dienoyl-CoA reductase + 3,-trans-enoyl-CoA isomerase FFA 3-Hydroxyacyl-CoA (HADH) FADH Malate Malate Fumarase Fumarate Succinate Pyruvate Citrate synthase Oxaloacetate (SDHA) Succinate Pyruvate complex (DLAT1, PDHX, PDHa1) GTP Krebs Cycle Succinyl CoA synthetase Citrate (SUCLA, SUCLG) Aconitase (ACO) Succinyl CoA cis-aconitate Aconitase (ACO) Isocitrate Isocitrate (IDH3A) α-ketoglutarate α-ketoglutarate complex (OGDH) 3-Ketoacyl-CoA thiolase B Fold change over D Glucose (mg/dl) F Malonyl CoA (μm) 1.5 1..5 5 15 1 5.7.6.5.4.3..1. Fatty acid oxidation genes ACSL1 CPT1b CPT HADHA ACADM ACADSB ECHS1 HADH FFA (μm) 8 6 4 Triglycerides (μm) Fold change over 18 1 6 1.5 1..5 DLAT1 PDHX Krebs cycle genes Ketones (μm) PDH1a ACO IDH3A OGDH SUCLA 18 p=.3 15 1 9 6 3 SUCLG SDHA C E Fold Change over 5 4 3 1 F p=. Nppa F p=.1 p=.5 F F F G G G p=.13 Nppb F Chemical Shift (ppm) fed fasted fed fasted C4
Supplementary Figure 4 A B Heart Acyl-CoAs CoA acetyl propionyl succinyl itaconyl glutaryl Medium Chain C1:3 C1: C1:1 decanoyl Long Chain C1:1 lauroyl myristoyl C15/C14:1-OH C14-OH C16:3 C16: C16:1 palmitoyl C17:1 linolenoyl linoleoyl oleoyl stearoyl C19: C19:1 C19 Very Long Chain C:5 C: C:1 -. C1:3 C1: C1:1 C1 C:6 C:5 C:4 C:3 C: C:1.. Liver Acyl-CoAs CoA acetyl propionyl succinyl itaconyl glutaryl Medium Chain C1:3 C1: C1:1 decanoyl Long Chain C1:1 lauroyl myristoyl C15/C14:1-OH C14-OH C16:3 C16: C16:1 palmitoyl C17:1 linolenoyl linoleoyl oleoyl stearoyl C19: C19:1 C19 Very Long Chain -. C Insulin (ng/ml) 5 4 3 1 p=.31 p=.1.. p=.5 D Adiponectin (μg/ml) 5 15 1 5 E Plasma T4 (μg/dl) 5 4 3 1 p=.34 p=. F Plasma corticosterone (ng/ml) 1 9 6 3 p=. p=.5 G Plasma BNP (pg/ml) 5 4 3 1 p=.4 p=.46 H Plasma ANP (pg/ml) 9 6 3 p=.14 p=.5
Supplementary Figure 5 Week * * Weight ± SEM (g) 15.5 ±.3 15.8 ±.4 1.5 ±.8 1.4 ±.9 Week 7 Weight ± SEM (g) 18.8 ±.4 17.4 ±.4# 16. ±.6* 16. ±.5* Isotypic parabiosis Heterotypic parabiosis Isotypic parabiosis
Acylcarnitines in liver from fed and fasted and MED13cTg mice. C6.159 ±..5 ±.4 #.1 ±. *. ±.3 # C5-OH/C3-DC.18 ±.1.71 ±.1 #.94 ±.13.67 ±.3 # C4-DC/Ci4-DC.48 ±.3.7 ±.4 #.38 ±.4 *.3 ±.5 C8:1.3 ±.7. ±..3 ±..3 ±. C8.6 ±.4.41 ±.3 #.51 ±.5.3 ±.3 # C6-DC/C8-OH.141 ±.1.7 ±.8 #.7 ±.11 *.37 ±.33 # C1:3.5 ±.1. ±.4 #.3 ±.. ±. # C1.4 ±.3.16 ±.3.19 ±.3.17 ±. C8:1-DC.1 ±.1.8 ±.1.6 ±.1 *.13 ±.1 # C1-OH/C8-DC.6 ±.1.6 ±.1.3 ±.1 *.9 ±.1 # C1:1.5 ±.1.3 ±.1 #. ±. *.3 ±. C1.8 ±.1.8 ±.1.5 ±.1 *.8 ±.1 # C14:1.15 ±.4.13 ±.3.6 ±.1 *.1 ±.1 # C14.4 ±.4.6 ±.4.1 ±. *.4 ±. # C16:.8 ±.1.6 ±.1.5 ±.1 *.7 ±.1 C16:1.43 ±.1.49 ±.11.1 ±.1 *.4 ±.4 # C16.16 ±..18 ±.17 #.5 ±.7 *.177 ±.13 # C18:.56 ±.1.86 ±.1.3 ±.4 *.19 ±.9 # C18.69 ±..13 ±.5 #.6 ±.4 *.114 ±.3 #
Acyl-CoAs in liver from fed and fasted and MED13cTg mice. CoA 67.74 ± 49.8 56.66 ± 65. 68.1 ± 43.57 461.86 ± 37.4 # Acetyl 865. ± 13.65 17.68 ± 381.5 # 395.4 ± 33.3 165.1 ± 83.65 # Propionyl 68.78 ± 19.4 41.51 ± 4.13 459.44 ± 64.43 * 34.3 ± 5.89 # Crotonyl 59.5 ± 5.65 9.66 ± 1.56 89.31 ± 4.98 * 1.57 ± 13.4 # C1:1 8.87 ± 5.73 17.5 ± 3.79 15.4 ± 3.9 1.15 ± 4. decanoyl 65.73 ± 6.83 55.31 ± 11.9 56.3 ± 1.48 5.1 ± 14.74 C1:1 38. ± 8.34 19.77 ± 4.71 9.4 ± 11.6 9.45 ± 5.15 lauroyl 5.58 ± 1.51 9.83 ± 1.75 4.94 ± 8.65 * 38.7 ± 3.7 # myristoyl 5.69 ± 4.41 59.88 ± 8.3 53.31 ± 3.78 5.57 ± 1.89 C15/C14:1-OH 15.61 ±.11 19.64 ± 3.95 8. ±.54 15.15 ±.6 C16:1 166.55 ± 31.65 15.98 ± 8.3 14.16 ± 11. 13.7 ± 17.3 palmitoyl 16.39 ± 14.14 16.57 ± 8.31 93.45 ± 1.74 * 155.8 ± 8.59 C17:1 8.8 ± 4.9.48 ±.67 6.66 ± 6.35 19.6 ±.7 linolenoyl 87. ± 8.5 85.43 ± 11.34 66.8 ± 8.95 86.57 ± 5.3 linoleoyl 53.14 ± 84.43 # 91.84 ± 11.6 45.37 ± 48.3 * 978.35 ± 6.5 oleoyl 77.33 ± 146.3 79.61 ± 161.64 # 94.78 ± 8.1 * 563.79 ± 78.89 stearoyl 181.68 ± 34.83 33.68 ± 7.71 16.34 ± 3.7 13.73 ± 5.1 # C19: 5.45 ± 5.93 3.4 ± 6.6 9.18 ±.86 * 16.4 ± 4.8 C19:1 44.9 ± 11.3 47.14 ± 9.9 34.69 ±.89 36.74 ±.74 C:5 31.7 ±.49 7. ± 4.46 3.8 ± 3.7 9.5 ± 4.57 C: 1.48 ± 33.88 18.91 ± 69.1 157.5 ± 5.36 114.6 ± 1.4 C:1 176.64 ± 57.69 7. ± 34.55 6.8 ± 1.1 * 14.4 ± 3.13 # C1 4.66 ± 3.57 1.44 ± 4.4 # 14.9 ± 4.56 9.45 ± 4.43 C:5 31.14 ± 5.68 37.36 ± 14.84 5.46 ± 5.3 19.39 ± 4.64 C:4 37.38 ± 7.53 5. ± 4.8 41.87 ± 14.81 44.5 ± 1.89 C: 63.8 ± 14.78 35.18 ± 4.75 58.39 ± 6.61 5.89 ±.13 # C:1 147.35 ± 4.54 3.51 ± 4.89 # 67.85 ± 1.49 *.95 ± 5.65 #
Acylcarnitines in heart from fed and fasted and MED13cTg mice. C4/Ci4.6 ±.4.594 ±.3.334 ±.3 *.515 ±.7 # C6.9 ±.1.98 ±.1.4 ±.1 *.97 ±.1 # C8.31 ±.1.41 ±.1.7 ±. *.41 ±. # C1.36 ±.1.77 ±..7 ±. *.7 ±. # C1-OH/C8-DC.7 ±..13 ±. #.3 ±..11 ±. # C1:1.1 ±.1.39 ±.1.7 ±. *.9 ±. # C1.7 ±.3.14 ±.3.8 ±. *.119 ±.1 # C1:1-OH/C1:1-DC.7 ±..1 ±.. ±. *.1 ±. # C1-OH/C1-DC.1 ±..14 ±.. ±. *.19 ±. # C14:1.136 ±.5.44 ±.6.16 ±. *.8 ±.1 # C14.4 ±.1.54 ±.13. ±.1 *.53 ±.4 # C14:-OH/C1:-DC.9 ±..14 ±..4 ±. *.14 ±. # C14:1-OH/C1:1-DC.5 ±.1.49 ±.1.5 ±. *.54 ±.1 # C14-OH/C1-DC.3 ±.1.36 ±.1.3 ±. *.5 ±. # C16:.191 ±.5.315 ±.6.16 ±. *.333 ±.5 # C16:1.38 ±.16.781 ±.. ±.1 *.816 ±.9 # C16.674 ±.31 1.81 ±.54.51 ±.1 *.368 ±.33 # C16-OH/C14-DC.54 ±..16 ±.3.7 ±. *.193 ±. # C18:3.56 ±..69 ±.1.6 ±. *.96 ±. # C18:.77 ±. 1.4 ±.36.51 ±.1 * 1.989 ±.4 # C18:1.889 ±.37.163 ±.61.16 ±.1 *.85 ±.45 # C18.88 ±.1.69 ±.17.3 ±.1 *.784 ±.11 # C:.54 ±.9.479 ±.13.18 ±.1 *.598 ±.1 # C:1.7 ±.11.466 ±.13.15 ±.1 *.56 ±.9 #
Acyl-CoAs in heart from fed and fasted and MED13cTg mice. CoA 71.6 ± 34.34 338.18 ± 3.1 179.54 ± 6.56 * 39.4 ± 7.67 # Acetyl 474.45 ± 93.18 37. ± 11. 687.53 ± 63. * 75.97 ± 7.43 # Propionyl 17.1 ± 4.5 3.98 ± 4.51 7.43 ± 3.93 * 16.69 ±.98 # Succinyl 57.54 ± 4.64 47.79 ± 8.8 79.84 ± 11.5 * 51.4 ± 6.7 # Itaconyl 4. ± 1.76 4.18 ± 1.44 6.5 ± 1.78 1.89 ±.43 # glutaryl 15.95 ± 1.91 11.1 ±.5 16.75 ±.98 11.1 ±.9 # C1:3 5.6 ± 1.14 1.88 ±.46 # 9.5 ± 1.7 * 3.6 ±.55 # C1: 3.54 ±.53 1.64 ± 1.1 1.89 ± 1.3 4.16 ± 1.18 C1:1 15.81 ± 3.56 18.8 ± 1.34 7.13 ±.1 * 4.5 ±.43 # decanoyl 38.34 ± 7.7 59.49 ± 8.1 19.95 ± 3.6 * 5.67 ± 4.85 # C1:1 8.4 ± 7.8 8.5 ± 5.38 16.6 ± 1.63 * 6.41 ± 1.9 # lauroyl 5.5 ± 13.9 63.7 ± 11.47 7.4 ± 3.6 * 59.1 ± 6.34 # myristoyl 76.7 ± 18.69 1.33 ± 18.84 3.77 ±.94 * 14.83 ± 8.66 # C15/C14:1-OH 14.86 ± 3.17 15.98 ±.3 9.37 ± 1.47 * 16.51 ± 1.57 # C14-OH 8.6 ± 1.91 9.35 ± 1.13 3.9 ±.49 * 1.45 ±.55 # C16:3 1.51 ± 5.6 19.3 ±.38 6.83 ± 1.6 * 7.78 ± 5.14 # C16: 15.37 ± 37.6 19.59 ± 13.47 61.55 ± 6.9 * 16.98 ± 19.8 # C16:1 33.9 ± 67.36 37.93 ± 58.76 69.14 ± 8.5 * 41. ± 8.5 # palmitoyl 67.85 ± 71.3 435.5 ± 57.45 11.6 ± 9.31 * 57.67 ± 59.63 # C17:1 7.31 ± 5.17 3.37 ±.87 18.19 ±.4 * 37.65 ± 3.4 # linolenoyl 18.16 ± 8.8 14.5 ± 15.86 44.19 ± 6.3 * 185. ± 33.51 # linoleoyl 885.3 ± 173.5 1.9 ± 91.81 347.38 ± 4. * 175.87 ± 34.11 # oleoyl 865.37 ± 39. 1456.93 ± 7. 85.47 ± 19.37 * 1999.5 ± 159.78 # stearoyl 17. ± 44.6 33.69 ± 18.74 133.51 ± 15.98 * 33.37 ± 37.5 # C19: 16.93 ± 3.53 3.6 ± 3.88 6.91 ± 1.69 * 3.84 ± 3.7 # C19:1 16.4 ± 3.76 16.38 ± 6.3 55.1 ± 6.5 * 187.37 ± 7. # C19 79.8 ± 18.68 97.96 ± 7.88 37.39 ± 6.46 * 149.15 ± 1.8 # C:5 5.18 ± 1.5 6.47 ±.7 1.76 ±.47 * 7.17 ± 1.19 # C: 354.75 ± 84.4 465.9 ± 3.43 14.58 ± 3.4 * 581.61 ± 75.8 # C:1 9.3 ± 68.53 331.3 ± 9.15 84.71 ± 13.94 * 49.89 ± 54.48 # C1:3 9. ± 1. 17.4 ± 4.58 3.11 ± 1.44 * 1.15 ±.6 # C1: 7.53 ± 1.99 17.34 ± 5.5 3.13 ± 1. * 1.6 ± 3.5 # C1:1 36.85 ± 8.74 4.91 ± 5. 4.7 ± 3. * 6.33 ± 1. # C1 31. ± 7.4 3. ± 4.9 19.4 ± 5.61 * 46.84 ± 6.73 # C:6 7.5 ± 1.78 6.7 ± 1.5 1.99 ± 3.4 9.71 ± 1.46 C:5 4.7 ± 1.48 5.88 ±.53.43 ±.76 4.55 ±.69 C:4 13.68 ± 4.19 1.3 ±. 5.63 ±.8 * 14.1 ±.6 # C:3.17 ± 3.8 1.18 ± 5.39 13.58 ±. * 5.74 ± 4.5 # C: 56.64 ± 14.63 65.15 ± 1.36 45.61 ± 16.4 7. ± 11.65 C:1 43.81 ± 8.16 48.97 ± 5.1 3.97 ± 7.8 48.91 ± 6.4
Acylcarnitines in serum from fed and fasted and MED13cTg mice. C 3.45 ±.8 43.736 ± 4.55 # 1.59 ± 1.98 4.331 ±.6 # C3 1.3 ±.14.63 ±.49 # 1.446 ±.119.68 ±.56 # C4/Ci4 1.67 ±.91 1.79 ±.18 # 1.5 ±.155.939 ±.116 C5:1.4 ±.5.39 ±.4 #.4 ±.5.4 ±.5 # C5.164 ±.1.168 ±.3.33 ±.1.188 ±.1 C4-OH.174 ±.19.476 ±.57 #.7 ±.4.489 ±.5 # C6.164 ±.19.199 ±.6.115 ±.15.179 ±.6 C5-OH/C3-DC.9 ±.15.169 ±.1 #.11 ±.17.18 ±.17 # C4-DC/Ci4-DC.53 ±.6.8 ±.11 #.65 ±.1.68 ±.14 C8:1.3 ±..9 ±. #. ±.3.1 ±. # C8.148 ±.38.35 ±.3 #.16 ±.49.35 ±.6 # C1-OH/C8-DC.156 ±.. ±. #.151 ±.49.3 ±.3 # C1:1.37 ±.6.45 ±.7.33 ±.9.48 ±.7 C1:-OH/C1:-DC.19 ±..4 ±.5 #.14 ±..39 ±.5 # C1:1-OH/C1:1-DC.34 ±.9.13 ±.1 #.3 ±.9.1 ±.14 # C1-OH/C1-DC.67 ±.8.134 ±. #.6 ±.8.136 ±.14 # C14.5 ±.1.168 ±.9 #.38 ±.13.151 ±.15 # C14:3-OH/C1:3-DC.4 ±.8.437 ±.4 #.48 ±.18.47 ±.39 # C14:-OH/C1:-DC.8 ±..5 ±.4 #.1 ±..7 ±.3 # C14-OH/C1-DC.65 ±.1.17 ±.16 #.71 ±.9.194 ±.16 # C16:3.94 ±.19.386 ±.33 #.98 ±.6.44 ±.9 # C16:-OH/C14:-DC.8 ±.6.37 ±.3 #. ±.6.38 ±.3 #
SUPPLEMENTARY FIGURE LEGENDS Figure S1. Cardiac overexpression of MED13 increases metabolic gene expression in white adipose tissue. (A) Schematic of changes in expression of genes involved in fatty acid transport and oxidation and the Krebs cycle. Red indicates increased gene expression in MED13cTg WAT, gene abbreviations are in parentheses and shown in graphical form in Figure 1. (B) Gene expression was also validated by qpcr, n=6. Data are mean + SEM and all genes shown in the graphs are significantly increased in MED13cTg WAT (p<.5), t-test. Related to Figure. Figure S. Regulation of liver metabolite production by cardiac expression of MED13 in the fed state. (A) Krebs cycle intermediary metabolites are unchanged in the fed state and are decreased in both and MED13cTg liver with fasting, but (B) are unchanged in the heart. (C) Ceramide species in the liver and (D) hearts of fed and fasted mice, n=5. Data are mean + SEM, two-way ANOVA followed by Tukey s test, *p<.5 fed vs. fed, #p<.5 fed vs. fasted. Related to Figure 3. Figure S3. Cardiac overexpression of MED13 alters metabolic gene expression. (A) Schematic of changes in expression of genes involved in fatty acid oxidation and the Krebs cycle. Green indicates decreased gene expression in MED13cTg heart, gene abbreviations are in parentheses and shown in graphical form in Figure 4. (B) Fatty acid oxidation and the Krebs cycle gene expression was validated by qpcr. All genes shown in the graphs are significantly decreased in MED13cTg heart (p<.5), t-test. (C) Nppa and Nppb gene expression trended to increase in MED13cTg hearts, irrespective of the fed or fasted state, n=5. (D) Blood glucose, free fatty acids (FFA), triglycerides, and ketones in the postprandial state, n=6. (E) Representative 13C-NMR spectrum of a perfused heart. The enlarged portion of the spectra shows the C4 glutamate peaks that arise from fatty acid oxidation (indicated by F) and glucose oxidation (indicated by G). (F) Malonyl CoA levels in and Med13cTg hearts in the fed and fasted state. Data are mean + SEM, t-test or two-way ANOVA followed by Dunnett s test. Related to Figure 4. Figure S4. MED13cTg hearts maintain the ability to adapt to fasting. (A) Acyl-CoA species in heart and (B) liver are decreased with fasting in MED13cTg mice. (C) Insulin, (D) adiponectin, (E) thyroxine (T4), (F) corticosterone, (G) brain natriuretic peptide (BNP), and (H) atrial natriuretic peptide (ANP) in serum from fed and fasted mice, n=5. Data are mean + SEM, two-way ANOVA followed by Tukey s test, *p<.5 fed vs. fed, #p<.5 fed vs. fasted. Related to Figure 5. Figure S5. Circulating factor(s) regulate enhanced WAT and liver metabolism and contribute to the lean phenotype of MED13cTg mice. Schematic and results of isotypic and heterotypic parabiosis experiments in and MED13cTg mice. Weights are from individual parabiots before surgery and 7 weeks post-surgery, n=6 pair per group. Data are mean ± SEM,
two-way ANOVA followed by Dunnett s test, *p<.5 vs., #p<.5 heterotypic parabiots vs. isotypic parabiots. Related to Figure 6. Supplementary Table 1. Acylcarnitines in liver from fed and fasted and MED13cTg mice. Acylcarnitines (µm) measured by metabolomics are mean ± SEM, two-way ANOVA followed by Tukey s test, n=5, *p<.5 fed vs. fed, #p<.5 fed vs. fasted. Supplementary Table. Acyl-CoAs in liver from fed and fasted and MED13cTg mice. Acyl-CoAs (pmol/ml) measured by metabolomics are mean ± SEM, two-way ANOVA followed by Tukey s test, n=5, *p<.5 fed vs. fed, #p<.5 fed vs. fasted. Supplementary Table 3. Acylcarnitines in heart from fed and fasted and MED13cTg mice. Acylcarnitines (µm) measured by metabolomics are mean ± SEM, two-way ANOVA followed by Tukey s test, n=5, *p<.5 fed vs. fed, #p<.5 fed vs. fasted. Supplementary Table 4. Acyl-CoAs in heart from fed and fasted and MED13cTg mice. Acyl-CoAs (pmol/ml) measured by metabolomics are mean ± SEM, two-way ANOVA followed by Tukey s test, n=5, *p<.5 fed vs. fed, #p<.5 fed vs. fasted. SupplementaryTable 5. Acylcarnitines in serum from fed and fasted and MED13cTg mice. Acylcarnitines (µm) measured by metabolomics are mean ± SEM, two-way ANOVA followed by Tukey s test, n=5, *p<.5 fed vs. fed, #p<.5 fed vs. fasted.